The main objective of this proposal is to develop efficacious immunotherapy for human B cell neoplasms employing anti- idiotype (anti-Id) monoclonal antibodies (MoAbs). The specific aims of this Phase I proposal are to develop anti-Id MoAbs to lymphoma and chronic lymphocytic leukemia (CLL) cross-reactive idiotopes. The availability of a panel of MoAbs to common tumor idiotopes suitable for the treatment of multiple patients would greatly enhance the practicality of anti-Id therapy. Anticommon Id MoAbs with the highest frequency of tumor cross-reactivity and with acceptable corresponding serum idiotope levels (is less than 50 ug/ml) will be chosen for future use in human clinical trials during the Phase 2 period. These clinical studies will employ a multi-modality approach incorporating anti-Id MoAbs conjugated to cytotoxic radioisotopes or administered in conjunction with other biological response modifiers. Overall, the results of the Phase 1 and 2 studies should lead to the practical development of anti-Id MoAb immunotherapies which may find future application in the treatment of human B cell lymphoma and CLL.